1. Field of Invention
This invention relates to a novel process for the preparation of carbinols by the reduction of a carboxylic acid or carboxylic acid anhydride group in organic compounds containing one or more such groups. More particularly, this invention provides a process for the preparation of carbinols whereby an organic compound containing a carboxylic acid or carboxylic acid anhydride group, an alkali metal borohydride, and a boron trihalide are contacted in a liquid medium in which diborane is soluble in the form of a labile borane adduct. Hydrolysis of the resulting reaction mixture then yields the corresponding carbinol formed by hydrogenation of the carboxylic acid or carboxylic acid anhydride group.
2. Description of the Prior Art
In U.S. Pat. No. 2,856,428, Herbert C. Brown disclosed that the addition of relatively minor amounts of aluminium chloride to solutions of sodium borohydride in the dimethyl ether of diethylene glycol (diglyme) greatly increases the reducing rates and capacities of the borohydride. This reagent rapidly reduces aldehyde, ketone, ester, carboxylic acid, nitrile, and amide groups. The reagent described by Brown consisted of an alkali metal borohydride and a halide of a polyvalent metal having a valence greater than two and less than six, such as aluminium chloride, gallium chloride, etc., in a liquid carrier such as diglyme. These reagents described by Brown did not include halides of metalloids, such as boron trihalides. The addition of a stoichiometric quantity of a boron trihalide to a solution of an alkali metal borohydride in diglyme results in the rapid evolution of diborane with the expected loss of the active hydride of the solution. Consequently, such a reagent is inoperative for reducing and hydrogenating chemical compounds.
Brown has disclosed in U.S. Pat. No. 2,945,886 that a reagent consisting of a boron trihalide and an alkali metal borohydride is exceedingly effective, under certain specific conditions, in enhancing the reducing properties of alkali metal borohydrides. Conspicuously omitted from this U.S. Pat. No. 2,945,886 was any discussion of the use of this procedure to reduce the carboxylic acid group.
The process claimed in U.S. Pat. No. 2,945,886 comprises reducing a chemical compound having a nitrile group by associating, in a inert liquid carrier, one component of a reagent consisting of an alkali metal borohydride and a boron trihalide with the other component of the reagent in the presence of the compound to be reduced. Thus, a mixture of a boron trihalide and the compound to be reduced, specifically a nitrile containing compound, is added slowly to a solution of the alkali metal borohydride. Alternatively, the boron trihalide is added slowly to a solution of the alkali metal borohydride containing the nitrile substituted compound. Serious disadvantages exist in this process. The recommended solvent, diglyme, is relatively expensive and thus limits the large scale commercial utility of this process. Also, the process is limited to functional groups which react rapidly with the diborane as formed, otherwise the diborane would vaporize away from the reaction mixture and cause serious problems.
The process of reducing a chemical compound having a reducible functional group by adding the compound to a reagent in which an alkali metal borohydride and a boron trihalide are previously combined in a liquid carrier is not described by Brown in U.S. Pat. No. 2,945,886.
The reaction of sodium borohydride dissolved in diglyme with boron trifluoride is known to generate diborane gas, B.sub.2 H.sub.6, an extremely useful chemical with many remarkable properties (H. C. Brown, Hydroboration, W.A. Benjamin, Inc., New York, New York, 1962). Diborane is an exceedingly powerful, but selective hydrogenating agent for functional groups as disclosed by Brown in U.S. Pat. No. 2,874,165 and in his recent book Boranes in Organic Chemistry, Cornell University Press, Ithaca, New York, 1972. Brown and Rao in J. Am. Chem. Soc., 82, 681 (1960) disclose diborane preformed by reaction of sodium borohydride and boron trifluoride etherate in diglyme in a separate vessel and passed over as a gas to a reaction vessel for use in reducing carboxylic acids in diglyme or tetrahydrofuran.
Diborane is a highly reactive gas which rapidly decomposes on exposure to air and moisture. Consequently, it is difficult to handle. Fortunately, diborane is highly soluble in tetrahydrofuran where it exists in the form of a labile borane-tetrahydrofuran adduct of the formula: ##SPC1##
This adduct formation greatly increases the solubility of diborane in tetrahydrofuran and makes it possible to prepare and ship solutions which are up to one molar in borane (BH.sub.3). In other common ether solvents, which do not readily form an ether-borane adduct, the solubility of diborane is quite low. Examples include diethyl ether, diisopropyl ether, and diglyme. Borane reductions performed in such solvents are potentially very dangerous because of the possibility of escape of diborane gas from the reduction media.
Brown has disclosed in U.S. Pat. No. 3,634,277 that the borane-tetrahydrofuran solutions can be prepared without handling the gas by treating suspensions of sodium borohydride in tetrahydrofuran with boron trifluoride followed by filtering or centrifuging the tetrahydrofuran solution of the borane-tetrahydrofuran complex from the precipitated sodium tetrafluoroborate. These borane-tetrahydrofuran solutions have been found to be useful for selective hydrogenations and reductions [H. C. Brown, P. Heim, and N. M. Yoon, J. Am. Chem. Soc., 92, 1637 (1970)].
In a copending application Ser. No. 334,642, filed Feb. 22, 1973, now U.S. Pat. No. 3,882,037, the entire contents of which is incorporated herein by reference by permission of the assignee, Herbert C. Brown disclosed that the presence of an aliphatic, alicyclic, or cyclic sulfide greatly stabilizes the borane-tetrahydrofuran reagent permitting the storage of such solutions for long periods of time at ambient temperatures. Such stabilized solutions can be prepared without handling diborane gas by treating a suspension of an ionic borohydride in tetrahydrofuran, containing an aliphatic, alicyclic, or cyclic sulfide, with boron trifluoride, followed by removal at ambient temperatures of the precipitated sodium tetrafluoroborate.
The solutions of labile borane complexes in tetrahydrofuran are the most convenient reagents to use for borane reductions on a laboratory scale. Unfortunately, major difficulties arise when these solutions of labile borane complexes in tetrahydrofuran are applied to large scale commercial reductions of chemical compounds. Since the vapor pressure of diborane above these tetrahydrofuran solutions is relatively high, the solutions are usually manufactured in relatively low concentrations not exceeding one molar in BH.sub.3. This means that large amounts of solvent must be handled and transferred for a relatively small quantity of borane. Another disadvantage of such a dilute solution is that the amount of organic compound that can be reduced per unit batch size is severely limited by the dilute concentration of the borane.
The most serious difficulties which limit the use of the tetrahydrofuran solutions of labile borane complexes for lage scale commercial reductions, result from the problems associated wih the processing of the mixtures to remove the solid sodium tetrafluoroborate. Because these borane solutions are extremely air-sensitive, specialized filtration and centrifugation process equipment is required along with specialized handling and transfer techniques. But even with the most careful processing procedures there is always an unavoidable loss of "active hydride" during these manipulations. This loss of active hydride is caused by the volatility of diborane and by the difficulty and virtual impossibility of achieving and maintaining thoroughly dry process equipment, thoroughly dry filters and completely air-tight systems. Another problem is the incompatibility of labile borane complexes with many commercial filters. For example, cellulose-derived filters cannot be used because of the presence of active hydrogens in this material. Also tetrahydrofuran is an excellent solvent for polymeric materials. Therefore, the choice of filter material is further limited. But an even more serious limitation which results from the superior solvent properties of tetrahydrofuran is that no known elastomers will withstand prolonged contact with tetrahydrofuran. Consequently, none of the gaskets in the filtration or centrifugation equipment can be made from the common, normally utilized Viton, buta-N, neoprene, or natural rubber elastomers. Economically, the processing required to remove the solid sodium tetrafluoroborate is a disadvantage because it is very time consuming and therefore quite expensive. Also, some of the active hydride content of the mixture is always lost in the removed solid material.
All of these disadvantages and difficulties have now been overcome by the use of the present invention.